ArticleAmerican journal of human genetics2015
Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes.
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Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 75 citations in OpenAlex.
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- Laryngo-tracheal stenosis in a woman with ablepharon macrostomia syndrome.BMC pulmonary medicine · 2019Article
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- Recessive MYF5 Mutations Cause External Ophthalmoplegia, Rib, and Vertebral Anomalies.American journal of human genetics · 2018Article
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Authors and funding
47 authors at 20 institutions in 12 countries.
Shannon MarchegianiNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH and National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA; Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, MD 20892, USA.
Taylor DavisNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH and National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
Federico TessadoriHubrecht Institute-KNAW and University Medical Centre Utrecht, 3584 CT Utrecht, the Netherlands.
Gijs van HaaftenDepartment of Medical Genetics, University Medical Center Utrecht, 3508 AB Utrecht, the Netherlands.
Francesco BrancatiDepartment of Medical, Oral, and Biotechnological Sciences, University of G. d' Annunzio Chieti and Pescara, Chieti 66100, Italy.
Alexander HoischenDepartment of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Haigen HuangDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Elise ValkanasNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH and National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
Barbara PuseyNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH and National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
Denny SchanzeMedizinische Fakultät und Universitätsklinikum Magdeburg, Institute of Human Genetics, 39120 Magdeburg, Germany.
Hanka VenselaarDepartment of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Anneke T Vulto-van SilfhoutDepartment of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Lynne A WolfeNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH and National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA; Office of the Clinical Director, National Human Genome Research Institute/NIH, Bethesda, MD 20892, USA.
Cynthia J TifftNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH and National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA; Office of the Clinical Director, National Human Genome Research Institute/NIH, Bethesda, MD 20892, USA.
Patricia M ZerfasOffice of Research Services, Division of Veterinary Resources, NIH, Bethesda, MD 20892, USA.
Giovanna ZambrunoLaboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata IDI-IRCCS, Rome 00167, Italy.
Ariana KariminejadKariminejad-Najmabadi Pathology and Genetics Center, Tehran 14667, Iran.
Farahnaz Sabbagh-KermaniKerman University of Medical Sciences, Kerman 76175, Iran.
Janice LeeNational Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA.
Maria G TsokosLaboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Chyi-Chia R LeeLaboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Victor FerrazDepartamento de Genetica, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Sao Paulo 14049, Brazil.
Eduarda Morgana da SilvaDepartamento de Genetica, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Sao Paulo 14049, Brazil.
Cathy A StevensDepartment of Medical Genetics, T.C. Thompson Children's Hospital, Chattanooga, TN 37403, USA.
Nathalie RocheDepartment of Plastic and Reconstructive Surgery, University Hospital of Ghent, Ghent 9000, Belgium.
Oliver BartschInstitute of Human Genetics, Johannes Gutenberg University, Mainz 55131, Germany.
Peter FarndonClinical Genetics Unit, Birmingham Women's Healthcare Trust, Birmingham B15 2TG, UK.
Eva Bermejo-SanchezECEMC (Spanish Collaborative Study of Congenital Malformations), CIAC, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III; and CIBER de Enfermedades Raras (CIBERER)-U724, Madrid 28029, Spain.
Brian P BrooksUnit on Pediatric, Developmental, and Genetic Eye Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA.
Valerie MaduroNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH and National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
Bruno DallapiccolaDepartment of Medical Genetics, Bambino Gesù Children's Hospital, IRCCS, Rome 00165, Italy.
Feliciano J RamosUnidad de Genética Médica, Servicio de Pediatría, GCV-CIBERER Hospital Clínico Universitario "Lozano Blesa," Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza, Spain.
Hon-Yin Brian ChungDepartment of Paediatrics and Adolescent Medicine, Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Cédric Le CaignecService de genetique medicale, CHU Nantes, 44093 Nantes, France and Inserm, UMR957, Faculté de Médecine, 44093 Nantes, France.
Fabiana MartinsSpecial Care Dentistry Center, Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo 05508-070, Brazil.
Witold K JacykDepartment of Dermatology, University of Pretoria, Pretoria 0028, Republic of South Africa.
Laura MazzantiDepartment of Pediatrics, S. Orsola-Malpighi Hospital University of Bologna, 40138 Bologna, Italy.
Han G BrunnerDepartment of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Department of Clinical Genetics, Maastricht University Medical Center, PO Box 5800, 6202AZ Maastricht, the Netherlands.
Jeroen BakkersHubrecht Institute-KNAW and University Medical Centre Utrecht, 3584 CT Utrecht, the Netherlands.
Shuo LinDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
May Christine V MalicdanNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH and National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA; Office of the Clinical Director, National Human Genome Research Institute/NIH, Bethesda, MD 20892, USA. Electronic address: malicdanm@mail.nih.gov.
Cornelius F BoerkoelNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH and National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
William A GahlNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH and National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA; Office of the Clinical Director, National Human Genome Research Institute/NIH, Bethesda, MD 20892, USA. Electronic address: gahlw@helix.nih.gov.
Bert B A de VriesDepartment of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Mieke M van HaelstDepartment of Medical Genetics, University Medical Center Utrecht, 3508 AB Utrecht, the Netherlands.
Martin ZenkerMedizinische Fakultät und Universitätsklinikum Magdeburg, Institute of Human Genetics, 39120 Magdeburg, Germany.
Thomas C MarkelloNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH and National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
Office of the Director · USNational Human Genome Research Institute · USRadboud University Medical Center · NLUniversidade de São Paulo · BRHubrecht Institute for Developmental Biology and Stem Cell Research · NLNational Cancer Institute · USUniversity Hospital Magdeburg · DEUniversity Medical Center Utrecht · NLUniversity of California, Los Angeles · USBambino Gesù Children's Hospital · ITBirmingham Women's Hospital · GBCentre for Biomedical Network Research on Rare Diseases · ESChildren’s Hospital at Erlanger · USGhent University Hospital · BEInserm · FRIstituto Dermopatico dell'Immacolata · ITJohannes Gutenberg University Mainz · DEKerman University of Medical Sciences · IRNational Eye Institute · USNational Institute of Dental and Craniofacial Research · US
Funding
NHGRI/DIR Clinical Support ServicesZIDHG200352 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI SOLOMON, BENJAMIN · 2009 to 2025
$182.8MHuman Biochemical GeneticsZIAHG000215 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM · 2009 to 2025
$72.6MCraniofacial Anomalies and RegenerationZIADE000746 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI LEE, JANICE · 2015 to 2025
$12.3MOphthalmic Genetics FellowshipZIEEY000477 · NEI · NATIONAL EYE INSTITUTE · PI HURYN, LARYSSA · 2009 to 2025
$7.2MStudy of Undiagnosed Diseases Genes in ZebrafishR21GM109908 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LIN, SHUO · 2014 to 2015
$462kNIGMS NIH HHS R21 GM109908
Abstract
Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations. We identified a recurrent de novo mutation in TWIST2 in seven independent AMS-affected families, as well as another recurrent de novo mutation affecting the same amino acid in ten independent BSS-affected families. Moreover, a genotype-phenotype correlation was observed, because the two syndromes differed based solely upon the nature of the substituting amino acid: a lysine at TWIST2 residue 75 resulted in AMS, whereas a glutamine or alanine yielded BSS. TWIST2 encodes a basic helix-loop-helix transcription factor that regulates the development of mesenchymal tissues. All identified mutations fell in the basic domain of TWIST2 and altered the DNA-binding pattern of Flag-TWIST2 in HeLa cells. Comparison of wild-type and mutant TWIST2 expressed in zebrafish identified abnormal developmental phenotypes and widespread transcriptome changes. Our results suggest that autosomal-dominant TWIST2 mutations cause AMS or BSS by inducing protean effects on the transcription factor's DNA binding.
Indexed as
Models, MolecularPhenotypeAbnormalities, MultipleAmino Acid SequenceAnimalsBase SequenceChromatin ImmunoprecipitationExomeEye AbnormalitiesEyelid DiseasesHeLa CellsHirsutismHumansHypertelorismHypertrichosisMacrostomiaRepressor ProteinsTWIST2 protein, humanTwist-Related Protein 1
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